Publications

Clinical Trials of Direct Thrombin Inhibitors During Invasive Procedures

No abstract is provided for this article.

Long-Term Clinical Results Following Stenting of the Left Main Stem

Objectives We investigated the long-term clinical outcomes and independent predictors of major cardiac events in unprotected left main coronary artery disease (ULMCA) patients treated by percutaneous coronary intervention with drug-eluting stent (DES). Background There is limited information on long-term (>3 years) outcomes after DES implantation for ULMCA. Furthermore, bifurcation angle and SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score are emerging as parameters for patient risk stratification, and their prognostic implications have still to be elucidated. Methods One hundred forty-eight patients with ULMCA treated with DES were analyzed and compared with a historical cohort of 79 patients who received bare-metal stents for the treatment of ULMCA. Patient-oriented composite end point was defined as the occurrence of all-cause death, any myocardial infarction, or any revascularization. Results The 4-year cumulative incidence of all-cause death, any myocardial infarction, any revascularization, and patient-oriented composite were 35.6%, 3.8%, 25.2%, and 54.4%, respectively. These end points had relatively increased from 1 year to 4 years by Δ70%, Δ5%, Δ50%, and Δ68%, respectively. When compared with a historical cohort who received bare-metal stents for ULMCA treatment, landmark analysis performed after the first 2 years of follow-up demonstrated that the DES cohort had significantly higher patient-oriented composite end point over the last 2 years of follow-up (26% vs. 8%, p = 0.02). EuroSCORE (European System for Cardiac Operative Risk Evaluation), cardiogenic shock, and SYNTAX score were identified as independent predictors for the 4-year patient-oriented composite, whereas bifurcation angle was not. Conclusions Late increase in patient-oriented composite end points after DES implantation for ULMCA warrants careful and long-term follow-up. SYNTAX score and EuroSCORE appear to have a significant prognostic value in long-term patient risk.

Effect of a Paf antagonist, WEB 2086, on airway microvascular leakage in the guinea‐pig and platelet aggregation in man

The triazolodiazepine WEB 2086 has been evaluated as an antagonist of platelet‐activating factor (Paf) by studying its effects on Paf‐induced human platelet aggregation and microvascular leakage in guinea‐pigs. WEB 2086 inhibited Paf‐induced platelet aggregation in platelet‐rich plasma in vitro (IC 50 = 117 ± 35 n m , mean ± s.d.) but had no effect on adenosine 3′,5′‐diphosphate‐induced aggregation. Paf‐induced microvascular leakage, measured by the extravasation of intravenously‐injected Evans blue dye, was inhibited in a dose‐related fashion in the airways and other tissues by WEB 2086, achieving a maximal inhibitory effect at 10 μg kg −1 , i.v. However, WEB 2086 (10 μg kg −1 , i.v.) did not inhibit a comparable increase in vascular permeability induced by ovalbumin in sensitized guinea‐pigs. We conclude that WEB 2086 is a potent antagonist of Paf and that Paf does not appear to be responsible for antigen‐induced microvascular leakage.

Quantitative Assessment of Aortic Regurgitation After Transcatheter Aortic Valve Replacement With Videodensitometry in a Large, Real-World Study Population

No abstract is provided for this article.

Tensile Behaviour of Waam High Strength Steel Material and Members

Wire arc additive manufacturing (WAAM), a method of metal 3D printing, has the capacity to create large scale elements suitable for construction applications with a high degree of design freedom and structural efficiency. There is currently however a lack of fundamental experimental data on the material and structural performance of such elements. Towards addressing this limitation, the tensile behaviour of WAAM high strength steel produced using different printing strategies is the focus of the present study. WAAM steel plates and tubular tension members manufactured with different interpass temperatures and toolpaths using ER110S-G welding wire were examined. A total of 60 tensile coupons, consisting of 40 as-built and 20 machined specimens, and 8 as-built circular hollow section (CHS) tension members, were tested. The examined WAAM materials were found to exhibit very little anisotropy, corroborated by a nearly homogeneous crystallographic texture observed by microstructural analysis, while the inherent surface undulations were shown to result in a varying degree of reduction in the material stiffness, strength and ductility at different angles to the print layer orientation. The tension members showed good structural resistance, but a considerable reduction in ductility compared to the coupon tests, due to the greater geometric variability and manufacturing defects.

P53 Phosphoinositide-3 kinase and mek inhibition prevents uptake of bacteria by airway epithelial cells

<h3>Introduction</h3> Bacteria are associated with COPD exacerbations with <i>Haemophilus influenzae</i>, and <i>Streptococcus pneumoniae</i> being predominant. Airway epithelium can protect pathogens from host defences and antibiotic treatment by internalisation. The mechanisms of this are unclear but may involve phosphoinositide-3- kinase (PI3K), p38, and ERK pathways. This requires many primary cells and therefore a validated cell line model would be of benefit. Therefore, we compared uptake of pathogenic bacteria by airway epithelial cells from non-smokers and COPD patients with A549 and BEAS-2B cell lines and the effects of pathway inhibitors were examined. <h3>Methods</h3> Non-smoker (n=7) and COPD (n=8) primary airway epithelial cells, and cell lines (BEAS-2B and A549 n=5) were incubated with fluorescently-labelled, heat-killed, <i>H. influenzae</i>, <i>S. pneumoniae</i>, or <i>E. coli</i> for up to 72 hours and uptake fluorimetrically. Confocal microscopy was used to confirm internalisation of bacteria. CXCL8 release was measured using ELISA. Effects of pathway inhibitors were determined by pre-treating cells with increasing concentrations of LY294002 (PI3K inhibitor), VX745 (p38 inhibitor), or PD98059 (ERK pathway inhibitor). Cell viability was assessed by MTT assay. <h3>Results</h3> Primary airway epithelial cells internalised respiratory bacteria <i>spp.</i> but not <i>E. coli</i>, in a time-dependent manner, with COPD cells internalising more <i>H. influenzae</i> but not <i>S. pneumoniae</i> compared to non-smokers at 48 hour (<i>H. influenzae</i> Non-smoker: 0.97±0.23 <i>vs</i>. COPD: 2.49±0.7 RFU χ 10³, p&lt;0.05) and 72 hour (<i>H. influenzae</i> Non-smoker: 1.44±0.35 <i>vs</i>. COPD: 3.01±2.2 RFU χ 10³, p&lt;0.05). A549 cells engulfed more bacteria than primary cells but the responses of BEAS-2B cells were similar to COPD cells and were used for subsequent experiments. Uptake was inhibited by LY294002 and PD98059, but not VX745. Conversely VX745, but not LY294002 or PD98059 inhibited CXCL8 release (Table 1). None of the treatments affected cell viability. <h3>Conclusion</h3> COPD airway epithelial cells engulf more <i>H. influenzae</i> than cells from non-smokers and this can be modelled by BEAS-2B cells. Uptake appears to require PI3K and ERK pathways but not p38 although, p38 is required for cytokine release. These data suggest that PI3K or MEK inhibitors in combination with antibiotics might be a good therapeutic strategy to treat bacterial exacerbations and recolonisation in COPD.

Testing, numerical analysis and design of stainless steel equal-leg angle section beams

The stability and design of stainless steel equal-leg angle section members subjected to uniaxial bending are studied herein. An experimental investigation, comprising material testing, initial geometric imperfection measurements and physical tests on hot-rolled austenitic stainless steel equal-leg angle section beams is first presented. The test results are then used to validate shell finite element models developed within ABAQUS, which are in turn used to undertake numerical parametric studies that consider both hot-rolled and cold-formed equal-leg angle section beams in austenitic, duplex and ferritic stainless steel with a wide range of slenderness values. Recent studies have shown that for angles under major-axis bending, both lateral-torsional and local buckling can arise, while under minor-axis bending, lateral-torsional buckling and Brazier-type flattening can occur. When designing for major-axis bending according to Eurocode 3, both local and lateral-torsional buckling are considered; it is shown herein that equal-leg angle sections under major-axis bending can be designed using a normalised slenderness based on the minimum of the local and lateral-torsional elastic buckling moments, while also considering their ratio. Under minor-axis bending, however, in comparison with the current provisions in Eurocode 3 that only require cross-section checks, it is shown that both safer and more accurate resistance predictions can be achieved when account is taken for lateral-torsional buckling and Brazier-type flattening. New design proposals for stainless steel equal-leg angle section beams, covering both major- and minor-axis bending, are therefore developed. The proposed design rules offer substantially more accurate and consistent resistance predictions compared to existing codified design rules. The reliability of the new design provisions, with a recommended partial safety factor γM1=1.1, is verified following the procedure provided in EN 1990.

Hybrid intravascular imaging in the study of atherosclerosisx

Recent evidence from large-scale clinical trials has not only underscored the potential value of intravascular imaging in detecting plaque characteristics that are associated with disease progression but also demonstrated the poor predictive accuracy of intravascular imaging in identifying the lesions that will evolve and cause a future event. This limitation has been attributed to the fact that all the available intravascular imaging techniques are unable to provide a detailed and complete visualization of plaque pathology and identify features that are related with increased vulnerability. To overcome these drawbacks, fusion of intravascular imaging modalities with different strengths and weaknesses has been proposed. In this chapter we describe the available intravascular imaging techniques, discuss their limitations in the study of atherosclerosis, and present the hybrid intravascular approaches that have been developed for more complete and precise assessment of plaque pathology.

Virtual bench testing of new generation coronary stents: why would we want to publish this paper?

No abstract is provided for this article.

Nitric Oxide

Asthma management: can we further improve compliance and outcomes?

Guidelines on myocardial revascularization

No abstract is provided for this article.

Ultimate behaviour of steel beams with discrete lateral restraints

New drugs for asthma.

Extract: Asthma has now become one of the most common chronic diseases in industrialized countries and is predicted to increase throughout the world over the next decade, particularly in developing countries. Previously, asthma was viewed as a disease of bronchoconstriction (closing of the airways) and treated predominantly with bronchodilators (drugs which open up the airways), but more recently it has been seen as an inflammatory disease of the airways and the mainstay of modern management is treatment with inhaled corticosteroids. The airway inflammation in asthma is characterized by activation of mast cells, infiltration of eosinophils and increased activated T helper 2 (Th2) lymphocytes. Inhaled corticosteroids have revolutionized the management of asthma, leading to better control of asthma, reduced hospital admissions and a reduced mortality. Corticosteroids and long-acting beta2-agonists (salmeterol and formoterol) in fixed combination inhalers are currently the most effective therapy for asthma and are increasingly used in all patients with persistent symptoms.

Extracellular vesicles from COPD cells exhibit a miRNA profile that could spread senescence

Managing COPD

A simplified and reproducible method to size the mitral annulus: implications for transcatheter mitral valve replacement

Transcatheter mitral valve replacement (TMVR) provides definitive valve replacement through a minimally invasive procedure. In the setting of TMVR, it remains unclear how relevant the differences between different mitral annular (MA) diameters are. We sought to define a simplified and reproducible method to describe the MA size.Using cardiac computed tomography angiography (CTA) studies of 47 patients, 3D MA perimeter (P3D) was annotated. The aorto-mitral continuity was excluded from MA contour either by manual annotation (yielding a saddle-shape model) or by simple truncation at the medial and lateral trigones (yielding a D-shape model). The method of the least squares was used to generate the projected MA area (Aproj) and perimeter (Pproj). Intercommissural (IC) and septolateral (SL) diameters, Dmean = (IC diameter + SL diameter)/2, area-derived diameter (DArea = 2 x √(A/π)) and perimeter-derived diameter (DPerimeter = P/π) were measured. MA eccentricity, height, and calcification (MAC) were assessed. Thirty studies were re-read by the same and by another observer to test intra- and inter-observer reproducibility. Patients (age, 75 ± 12 years, 66% males) had a wide range of mitral regurgitation severity (none-trace in 8%, mild in 55%, moderate-severe in 37%), MA size (area: 5-16 cm2), eccentricity (-8-52%), and height (3-11 mm). MAC was seen in 11 cases, in whom MAC arc occupied 26 ± 20% of the MA circumference. DArea (36.0 ± 4.0 mm) and DPerimeter (37.1 ± 3.8 mm) correlated strongly (R2 = 0.97) and were not significantly different (P = 0.15). The IC (39.3 ± 4.6 mm) and the SL (31.4 ± 4.5 mm) diameters were significantly different from DArea (P < 0.001) while Dmean (35.4 ± 4.0 mm) was not (P = 0.5). The correlation of DArea was stronger with Dmean (R2 = 0.96) than with IC and SL diameters (R2 = 0.69 and 0.76, respectively). The average difference between DArea and Dmean was +0.6 mm and the 95% limits of agreement were 2.1 and -0.9 mm. Similar results were found when the D-shape model was applied. All MA diameters showed good reproducibility with high intraclass correlation coefficient (0.93-0.98), small average bias (0.37-1.1 mm), and low coefficient of variation (3-7%) for intra- and inter-observer comparisons. Reproducibility of DArea was lower in patients with MAC.MA sizing by CTA is readily feasible and reproducible. Dmean is a simple index that can be used to infer the effective MA size.

Peripheral vascular disease: shaping a new panvascular interventional approach

No abstract is provided for this article.

Analytical modelling of plastic collapse in compressed elliptical hollow sections